BACKGROUND Randomised trial protocols may incorporate interim analyses, with the potential to stop the study for futility if early data show insufficient promise of a treatment benefit. Previously, we have shown that this approach will theoretically lead to mis-estimation of the treatment effect. We now wished to ascertain the importance of this phenomenon in practice. METHODS We reviewed the methods and results in a set of trials that had stopped for futility, identified through an extensive literature search. We recorded clinical areas, interventions, study design, outcomes, trial setting, sponsorship, planned and actual treatment effects, sample sizes; power; and if there was a data safety monitoring board, or a published protocol. We identified: if interim analyses were pre-specified, and how many analyses actually occurred; what pre-specified criteria might define futility; if a futility analysis formed the basis for stopping; who made the decision to stop; and the conditional power of each study, i.e. the probability of statistically significant results if the study were to continue to its complete sample size. RESULTS We identified 52 eligible trials, covering many clinical areas. Most trials had multiple centres, tested drugs, and 40% were industry sponsored. There were 75% where at least one interim analysis was planned a priori; a majority had only one interim analysis, typically with about half the target total sample size. A majority of trials did not pre-define a stopping rule, and a variety of reasons were given for stopping. Few studies calculated and reported low conditional power to justify the early stop. When conditional power could be calculated, it was typically low, especially under the current trend hypothesis. However, under the original design hypothesis, a few studies had relatively high conditional power. Data collection often continued after the interim analysis. CONCLUSIONS Although other factors will typically be involved, we conclude that, from the perspective of conditional power, stopping early for futility was probably reasonable in most cases, but documentation of the basis for stopping was often missing or vague. Interpretation of truncated trials would be enhanced by improved reporting of stopping protocols, and of their actual execution.

中文翻译：

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对随机试验的系统调查，由于徒劳无功而提前停止。

背景技术随机试验方案可能会纳入临时分析，如果早期数据显示治疗益处的希望不足，则有可能因无效而停止研究。以前，我们已经表明，这种方法理论上会导致对治疗效果的错误估计。我们现在希望确定这种现象在实践中的重要性。方法我们通过大量文献检索确定了因徒劳而停止的一组试验中的方法和结果。我们记录了临床领域，干预措施，研究设计，结果，试验设置，赞助，计划和实际治疗效果，样本量；功率; 以及是否有数据安全监控委员会或已发布的协议。我们确定：是否预先指定了中期分析，以及实际发生了多少次分析？哪些预先规定的标准可以定义徒劳；无效性分析是否构成了停止的基础；谁决定停止；以及每项研究的条件效力，即，如果研究要继续达到其完整的样本量，则具有统计学显着性结果的概率。结果我们确定了52个合格的试验，涉及许多临床领域。大多数试验都有多个中心，经过测试的药物，其中40％由行业赞助。有75％的人至少事先进行了一项中期分析。大多数人只进行了一次中期分析，通常只有目标总样本量的一半左右。大多数试验并未预先定义停止规则，并且给出了多种停止原因。很少有研究计算出并报告较低的条件功率来证明提前停止的理由。当可以计算有条件能力时，通常较低，尤其是在当前趋势假设下。但是，在原始设计假设下，一些研究具有相对较高的条件能力。中期分析后，通常会继续收集数据。结论尽管通常会涉及其他因素，但我们得出的结论是，从有条件的权力的角度来看，在大多数情况下尽早停止徒劳可能是合理的，但停止依据的文献往往不多或含糊。通过改进停止协议及其实际执行的报告，可以提高对截断试验的解释。结论尽管通常会涉及其他因素，但我们得出的结论是，从有条件的权力的角度来看，在大多数情况下尽早停止徒劳可能是合理的，但停止依据的文献往往不多或含糊。通过改进停止协议及其实际执行的报告，可以提高对截断试验的解释。结论尽管通常会涉及其他因素，但我们得出的结论是，从有条件的权力的角度来看，在大多数情况下尽早停止徒劳可能是合理的，但停止依据的文献往往不多或含糊。通过改进停止协议及其实际执行的报告，可以提高对截断试验的解释。